CER-1236 in Patients With Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Myelofibrosis (MF)

CER-1236 is a first in class chimeric engulfment receptor T-cell therapy candidate that targets the Tim4 ligand.

This is a first in human, multi center, open label, phase 1/1b study to evaluate the safety and preliminary efficacy of CER-1236 in patients with relapsed/refractory (R/R), measurable residual disease (MRD) positive acute myeloid leukemia (AML), or TP53mut disease.

The study is divided into Part 1 (escalation phase) and Part 2 (expansion phase).

Part 1 (Escalation Phase): The primary objectives of Part 1 are to define the safety of different doses of CER-1236 and to define the recommended dose for Part 2 (RP2D) of CER-1236.

Part 2 (Expansion Phase): The objective of the Part 2 expansion cohort is to evaluate the safety and efficacy of CER-1236 in patients with acute myeloid leukemia.

• CER-1236 (Drug): an autologous chimeric engulfment receptor T-cell
• Cyclophosphamide (Drug): Lymphodepleting chemotherapy
• Fludarabine (Drug): Lymphodepleting chemotherapy
• Mesna (Drug): Chemoprotectant

Primary outcomes

• Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 1) [2 year]: Escalation Period
• Incidence of dose-limiting toxicities (DLTs) of CER-1236 Monotherapy - (Part 1) [28 days]: Escalation Period
• Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 2) [2 years]: Expansion Period

Secondary outcomes

• Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 1) [2 years]: Escalation Period
• PK (Cmax) of CER-1236 - (Part 1) [2 years]: Escalation Period
• PK (AUC) of CER-1236 - (Part 1) [2 year]: Escalation Period
• Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 2) [2 years]: Expansion Period

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria:

* Patients need to have a confirmed diagnosis of de novo or secondary AML, or myelodysplastic syndrome (MDS)/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification.
* Absolute lymphocyte count >0.3 x 109/L prior to apheresis.
* Eastern cooperative oncology group (ECOG) performance status 0 to 1.

Exclusion Criteria:

* Prior therapy with a permanently integrated, genetically modified cell product.
* No measurable leukemia on the screening bone marrow evaluation prior to any bridging therapy.
* Active autoimmune disease or history of autoimmune disease requiring treatment within the prior 2 years. Patients with history of autoimmune thyroiditis or type 1 diabetes well controlled on replacement regimen are eligible.
* A known hypersensitivity or severe allergy to fludarabine, cyclophosphamide, or study drug components or diluents.
* Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the physician.
* Primary immunodeficiency disorder.